Project reveals importance of cancer gene mutation testing

Jun. 8, 2017, 9:12 AM

An international genomic data-sharing consortium has analyzed nearly 19,000 patient genomic records and found that testing of patient tumors for relevant gene mutations often provides a roadmap for the use of effective therapies.

The American Association for Cancer Research (AACR) Genomics Evidence Neoplasia Information Exchange (GENIE) is a multi-phase, multi-year data-sharing project launched in 2015 with eight academic centers. Vanderbilt-Ingram Cancer Center (VICC) is one of the institutions that shared de-identified genomic records from patients treated at the center to determine if genome sequencing can identify clinically useful mutations.

Mia Levy, M.D., Ph.D., Ingram Professor of Cancer Research and director of Cancer Health Informatics and Strategy, and Christine Micheel, Ph.D., research assistant professor of Medicine and managing editor of My Cancer Genome, led the VICC effort. Thomas Stricker, M.D., Ph.D., Michele LeNoue-Newton, Ph.D., and Lucy Wang also served as authors.

Mia Levy, M.D., Ph.D.

One of the criticisms of molecular profiling is the time and financial cost involved in testing all patients since relatively small percentages of patients actually have a mutation that can be treated with a specific therapy. To determine the frequency of important mutations, the AACR Project GENIE group mapped all mutations to variant interpretations merged from other knowledge bases, including My Cancer Genome, OncoKB and Personalized Cancer Therapy.

The new analysis found that more than 30 percent of the patient samples had mutations that are clinically actionable, meaning patients potentially could be treated with targeted therapies already approved by the U.S. Food and Drug Administration (FDA) or which are being tested in clinical trials.

These frequencies varied widely across disease, from highly recurrent and druggable mutations in gastrointestinal stromal tumors (GIST) — 66 percent, almost all of which were mutations of KIT and PDGFRA associated with standard-of-care therapies — to tumor types with few actionable alterations, such as renal cell, prostate or pancreatic cancer.

Breast cancer is the disease with the highest fraction of patients who might benefit from existing investigational targeted therapies, due to frequent mutations of AKT1, ERBB2 and PIK3CA, account­ing for 38 percent of patients.

The investigators anticipate one of the benefits of GENIE will be an increased power for determining the clinical significance of mutations, particularly new indica­tions for approved drugs, as well as data-driven selection of tumors likely to contain actionable mutations for clinical trials.

The study was supported by funds from the AACR, Genentech, Boehringer Ingelheim, Pfizer, Eli Lilly, the Howard Hughes Medical Institute, the National Institutes of Health, the National Cancer Institute, the Princess Margaret Cancer Foundation, the Ontario Ministry of Health, Susan G. Komen, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the T.J. Martell Foundation, the Commonwealth Foundation, the Cancer Prevention and Research Institute of Texas, the Dutch Ministry of Health, and the Dutch Cancer Society.